Inflammation in atherosclerosis: pathophysiology and mechanisms

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(11)

Published: Nov. 11, 2024

Abstract Atherosclerosis imposes a heavy burden on cardiovascular health due to its indispensable role in the pathogenesis of disease (CVD) such as coronary artery and heart failure. Ample clinical experimental evidence has corroborated vital inflammation pathophysiology atherosclerosis. Hence, demand for preclinical research into atherosclerotic is horizon. Indeed, acquisition an in-depth knowledge molecular cellular mechanisms atherosclerosis should allow us identify novel therapeutic targets with translational merits. In this review, we aimed critically discuss speculate recently identified Moreover, delineated various signaling cascades proinflammatory responses macrophages other leukocytes that promote plaque end, highlighted potential targets, pros cons current interventions, well anti-inflammatory atheroprotective mechanisms.

Language: Английский

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Inhibition of IFITM3 in cerebrovascular endothelium alleviates Alzheimer's‐related phenotypes

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract INTRODUCTION Interferon‐induced transmembrane protein 3 (IFITM3) modulates γ‐secretase in Alzheimer's Disease (AD). Although IFITM3 knockout reduces amyloid β (Aβ) production, its cell‐specific effect on AD remains unclear. METHODS Single nucleus RNA sequencing (snRNA‐seq) was used to assess expression. Adeno‐associated virus‐BI30 (AAV‐BI30) injected reduce expression the cerebrovascular endothelial cells (CVECs). The effects phenotypes and mice were examined through behavioral tests, two‐photon imaging, flow cytometry, Western blot, immunohistochemistry, quantitative polymerase chain reaction assay (qPCR). RESULTS increased CVECs of patients with AD. Overexpression primary enhanced Aβ generation regulating beta‐site APP cleaving enzyme 1 (BACE1) γ‐secretase. further expression, creating a vicious cycle. Knockdown decreased accumulation within walls, reduced Alzheimer's‐related pathology, improved cognitive performance transgenic mice. DISCUSSION alleviates pathology impairment. Targeting holds promise for treatment. Highlights ( ) (CVECs) Cerebrovascular regulates deposits improves impairments could be potential target treatment

Language: Английский

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Exploring CAR-macrophages in non-tumor diseases: Therapeutic potential beyond cancer

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

After significant advancements in tumor treatment, personalized cell therapy based on chimeric antigen receptors (CAR) holds promise for transforming the management of various diseases. CAR-T therapy, first approved CAR product, has demonstrated therapeutic potential treating infectious diseases, autoimmune disorders, and fibrosis. CAR-macrophages (CAR-Ms) are emerging as a promising approach immune particularly solid highlighting feasibility using macrophages to eliminate pathogens abnormal cells.

Language: Английский

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Sulforaphane promotes diabetic wound healing by regulating macrophage efferocytosis and polarization

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114243 - 114243

Published: Feb. 11, 2025

Language: Английский

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Macrophage Heterogeneity and Efferocytosis: Beyond the M1/M2 Dichotomy

Circulation Research, Journal Year: 2024, Volume and Issue: 134(2), P. 186 - 188

Published: Jan. 18, 2024

Language: Английский

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SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 4, 2024

T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While indicates an active anti-viral response, is sign of poor prognosis. T-cells, essence, rarely express ACE2 receptors, making cause cell depletion enigmatic. Moreover, emerging strains posed immunological challenge, potentially alarming for next pandemic. Herein, we review how possible indirect direct key mechanisms could contribute SARS-CoV-2-associated-lymphopenia. The fundamental mechanism inflammatory cytokine storm elicited by viral infection, which alters host metabolism into more acidic state. This "hyperlactic acidemia" together suppresses T-cell proliferation triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results shift from steady-state hematopoiesis stress hematopoiesis. Even low expression, presence cholesterol-rich lipid rafts on activated T-cells may enhance entry syncytia formation. Finally, indicate participation other receptors or auxiliary proteins that can work alone concert mechanisms. Therefore, address CD147-a novel route-for its new variants. CD147 not only expressed but it interacts co-partners orchestrate various biological processes. Given these features, appealing candidate pathogenicity. Understanding molecular cellular behind SARS-CoV-2-associated-lymphopenia will aid discovery potential therapeutic targets improve resilience our immune system against this rapidly evolving virus.

Language: Английский

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The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3854 - 3854

Published: March 29, 2024

Macrophages (Mφs) play a crucial role in the homeostasis of periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote resolution multiple infected diseases via accelerating polarization into M2 type. However, efferocytosis–apical periodontitis (AP) relationship not elucidated yet. This study aimed explore pathogenesis AP. Clinical specimens were collected determine involvement region immunohistochemical and immunofluorescence staining. For further understanding moderator effect AP, both an vitro AP model vivo treated with ARA290, agonist. Histological staining, micro-ct, flow cytometry, RT-PCR Western blot analysis performed detect inflammatory status, alveolar bone loss related markers models. The data showed that is observed tissues enhancing ability could effectively facilitating polarization. Collectively, our demonstrates functional importance pathology highlights ARA290 serve as adjuvant therapeutic strategy for

Language: Английский

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Hydrogen Sulfide Modulation of Matrix Metalloproteinases and CD147/EMMPRIN: Mechanistic Pathways and Impact on Atherosclerosis Progression

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1951 - 1951

Published: Aug. 26, 2024

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation potential cardiovascular events. Key players in ECM inflammation are metalloproteinases (MMPs) CD147/EMMPRIN, surface glycoprotein expressed on cells, vascular smooth muscle cells (VSMCs), immune that regulates MMP activity. Hydrogen sulfide (H₂S), gaseous signaling molecule, has emerged as significant modulator of these processes including oxidative stress mitigation, reduction, remodeling. This systematic review investigates the mechanistic pathways through which H₂S influences MMPs CD147/EMMPRIN assesses its impact atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, Web Science databases, focusing studies examining modulation contexts. Findings indicate modulates expression activity transcriptional regulation post-translational modifications, S-sulfhydration. By mitigating stress, reduces activation, contributing stability also downregulates via pathways, diminishing responses cellular proliferation plaques. The dual regulatory role inhibiting downregulating CD147 suggests therapeutic agent stabilizing atherosclerotic plaques inflammation. Further research warranted elucidate precise molecular mechanisms explore H₂S-based therapies for clinical application atherosclerosis.

Language: Английский

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TRAF6 promotes abdominal aortic aneurysm development by activating macrophage pyroptosis via the NLRP3/Caspase1/GSDMD pathway

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 20, 2025

Abstract Abdominal aortic aneurysm represents a critical pathology of the aorta that currently lacks effective pharmacological interventions. TNF receptor‐associated factor 6 (TRAF6) has been established to be involved in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. However, its role abdominal (AAA) remains unclear. This study aimed explore TRAF6 on AAA formation underlying mechanisms. Single‐cell RNA sequencing human tissues demonstrated was significantly upregulated macrophages. Moreover, overexpression promotes elastase‐induced C57BL/6 mice, while inhibition could attenuate development. Consistently, macrophages through vitro methods notably limits their pyroptosis, also diminishing proinflammatory responses these cells. Mechanistically, can modulate macrophage pyroptosis NLRP3/Caspase1/GSDMD signaling pathway. Our highlights crucial TRAF6/NLRP3/Caspase1/GSDMD axis AAA, offering potential biomarkers therapeutic targets for AAA.

Language: Английский

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Cyclophilin–CD147 interaction enables SARS-CoV-2 infection of human monocytes and their activation via Toll-like receptors 7 and 8

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Monocytes and macrophages, as important constituents of the innate immune system, are equipped with multiple Toll-like-receptors (TLRs) to recognize invading pathogens, such SARS-CoV-2, mount an antiviral response. Nevertheless, their uncontrolled activation can lead hyperinflammation seen in severe COVID-19. Surprisingly, we observed that recombinant SARS-CoV-2 Spike (S) Nucleocapsid (N) proteins triggered only a weak proinflammatory response human peripheral blood monocytes. By employing THP-1 Jurkat NF-κB::eGFP reporter cell lines expressing specific TLRs, various TLR ligands blocking antibodies, determined surface including TLR2/1, TLR2/6 TLR4 do not play major role sensing. However, monocytes potently activated by replication-competent correlates viral uptake is monocytes, but lymphocytes. We show monocyte involves two distinct steps. Firstly, infects process independent S protein prime receptor angiotensin-converting enzyme 2. Instead, alternative CD147, which highly expressed on recognizes its well-known interaction partners cyclophilins A B incorporated into virions. Secondly, upon via cyclophilin-CD147 interaction, be inhibited CD147 antibodies or competition cyclophilin B, RNA recognized TLR7/8 endosomes, leading upregulation tumor necrosis factor (TNF), interleukin (IL)-1β IL-6, comprising core hyperinflammatory signature. Taken together, our data reveal novel mechanism how sense suggest targeting axis might beneficial alleviate overt myeloid-driven inflammation infection.

Language: Английский

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